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MAPT-Related Disorders.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2000 Nov 7 [updated 2010 Oct 26].

Author information

1
Department of Neurology, Erasmus Medical Center, Rotterdam, Netherlands
2
Department of Neurology, Havenziekenhuis, Rotterdam, Netherlands
3
Department of Clinical Genetics, Vrije Universiteit Medical Center, Amsterdam, Netherlands

Excerpt

CLINICAL CHARACTERISTICS:

The clinical manifestations of MAPT-related disorders (MAPT-related tauopathies) are most typically those of frontotemporal dementia (FTDP-17), but also include progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), mild late-onset parkinsonism, and dementia with epilepsy. Clinical presentation of frontotemporal dementia (FTD) is variable: some present with slowly progressive behavioral changes, language disturbances, and/or extrapyramidal signs, whereas others present with rigidity, bradykinesia, supranuclear palsy, and saccadic eye movement disorders. Onset is usually between ages 40 and 60 years, but may be earlier or later. The disease progresses over a few years into profound dementia with mutism. PSP is characterized by progressive vertical gaze palsy in combination with a prominent loss of balance at early stages of the disease. With progression, axial rigidity, dysarthria, and dysphagia become prominent, often in combination with a frontal dysexecutive syndrome. CBD is a progressive neurodegenerative disorder which affects both the frontoparietal cortex and the basal ganglia, resulting in a mild to moderate dementia in combination with asymmetric parkinsonism, ideomotor apraxia, aphasia, and an alien-hand syndrome.

DIAGNOSIS/TESTING:

The diagnosis of a MAPT- related disorder relies on: typical clinical findings; often on characteristic findings on neuroimaging, single-photon emission computed tomography (SPECT), or positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET); a positive family history; and most importantly, demonstration of a pathogenic variant in MAPT, the gene encoding the protein tau.

MANAGEMENT:

Treatment of manifestations: Sedative or antipsychotic drugs help to reduce extreme restlessness, roaming behavior, delusions, and hallucinations; seizures are treated in the customary manner. Psychological support for partners or other caregivers is essential. Extrapyramidal signs are usually unresponsive or only partially responsive to L-dopa treatment. Agents/circumstances to avoid: The selective serotonin reuptake inhibitor (SSRI) paroxetine may increase cognitive impairment in persons with FTD.

GENETIC COUNSELING:

MAPT-related disorders are inherited in an autosomal dominant manner. Most individuals diagnosed with a MAPT-related disorder have had an affected parent; however, because of the late onset and relatively rapid course of the disease, the affected parent has often died before onset of the disease in the offspring. De novo pathogenic variants are extremely rare. Each child of an individual with a MAPT-related disorder has a 50% chance of inheriting the pathogenic variant. Prenatal diagnosis for pregnancies at increased risk is possible when the disease-causing allele in the family is known; however, requests for prenatal diagnosis of (typically) adult-onset diseases are not common.

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